Effect of Steroids on Gene Expression in the Healthy Smokers Lungs

NCT00532584 | Withdrawn Phase 4

• 1 other identifier: 0709009398
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). The cells lining the lung airways (epithelium) and the cells on the surface of the epithelium (alveolar macrophages) of healthy smokers develop characteristic gene expression changes that are different from that of nonsmokers. These gene expression changes include up- and down-regulation of genes in functional categories known to be relevant to the development of COPD. Administration of anti-inflammatory medications (inhaled steroids) in combination with long acting medications that open the airways (bronchodilators), are known to decrease the rate of acute exacerbations and improve the quality of life of individuals with COPD; however, the mechanisms underlying these beneficial effects of are poorly understood. This study will assess the effect of traditional therapy for COPD (inhaled corticosteroids, an anti-inflammatory medication, plus a bronchodilator, a medication that helps open the airways) on smoking-induced gene changes in airway epithelium and alveolar macrophages. Volunteer subjects will be evaluated by bronchoscopy to sample lung cells at 0, 7 and 14 days, with the therapy given at day 1 through day 7. The bronchoscopy aspects of this study will be covered by approved Weill-Cornell IRB protocol # 0005004439 (see below.) To participate in this protocol, the research subject will first be enrolled in Weill-IRB protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy", fulfilling the inclusion/exclusion criteria of that protocol. They will be invited to participate in this protocol only if they meet the additional inclusion/exclusion criteria of this protocol.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD; inhaled steroids; bronchodilator; gene expression; smoker's lungs

Outcome Measures

Primary Outcomes (1)

• Microarray chips are scanned and analyzed using Affymatrix Microarray suite version 5 (MAS5). Using GeneSpring software the data is normalized and differential expression is determined using alveolar macrophages.

  Day 7 and Day 14 following initiation of therapy compared to baseline values obtained on screening

Secondary Outcomes (1)

• St. George Respiratory questionnaire

  To be completed on Screening Day

Study Arms (3)

treatment with inhaled beclomethasone

EXPERIMENTAL

The treatment with inhaled beclomethasone will be administered to Group A from Day 1 to Day 7 via a metered dose inhaler (QVAR 80 HFA) delivering 80 micrograms of beclomethasone per puff. QVAR will be purchased by the Department of Genetic Medicine. The dose will be 2 puffs twice a day for 7 days

Drug: Beclomethasone

Control - healthy smokers

NO INTERVENTION

Group B will act as control and include healthy smokers who receive no treatment.

control - healthy non-smokers

NO INTERVENTION

Group C will act as control and include healthy non-smokers who receive no treatment.

Interventions

Beclomethasone DRUG

The treatment with inhaled beclomethasone will be administered to Group A from Day 1 to Day 7 via a metered dose inhaler (QVAR 80 HFA) delivering 80 micrograms of beclomethasone per puff. QVAR will be purchased by the Department of Genetic Medicine. The dose will be 2 puffs twice a day for 7 days

treatment with inhaled beclomethasone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group A and B
• All study individual should be enrolled in Weill-IRB protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy"
• All study subjects should be able to provide informed consent
• Current smokers with 15-to 40 pack-year history
• All study individuals should be healthy as per protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy"
• Group C
• All study individual should be enrolled in Weill-IRB protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy"
• All study subjects should be able to provide informed consent
• All study individual should be healthy as per protocol #0005004439 entitled "Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy"

You may not qualify if:

• Group A and B
• Smokers intending to quit smoking in the next 14 days.
• Individuals already receiving any lung related inhalers
• Females who are pregnant or nursing
• Group C
• Non-smokers who intend to start smoking in the next 14 days
• Individuals already receiving any lung related inhalers
• Females who are pregnant or nursing

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Beclomethasone

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated

Study Officials

• Ann E Tilley, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2007
• First Posted: September 20, 2007
• Study Start: February 1, 2011
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: May 4, 2016

Record last verified: 2016-05

Locations

US (1)